Mass spectrometers employing atmospheric pressure electrospray ionization (ESI) have been demonstrated to be particularly useful for obtaining mass spectra from liquid samples and have widespread application. ESI has been used with quadrupole, magnetic and electric sector, Fourier transform, ion trap, and time-of-flight mass spectrometers. ESI mass spectrometry (MS) is frequently used in conjunction with high performance liquid chromatography (HPLC), and combined HPLC/ESI-MS systems are commonly used in the analysis of polar and ionic species, including biomolecular species. ESI has also been used as a MS interface with capillary electrophoresis (CE), supercritical fluid chromatography (SFC), and ion chromatography (IC). ESI-MS systems are particularly useful for transferring relatively nonvolatile and high molecular weight compounds such proteins, peptides, nucleic acids, carbohydrates, and other fragile or thermally labile compounds from the liquid phase to the gas phase while also ionizing the compounds.
ESI is a “soft” or “mild” ionization technique that generates a charged dispersion or aerosol at or near atmospheric pressure and typically at ambient temperature. Since ESI generally operates at ambient temperatures, labile and polar samples may be ionized without thermal degradation, and the mild ionization conditions generally result in little or no fragmentation. Typically, the aerosol is produced in an ionization chamber by passing the liquid sample containing solvent and analyte through an electrospray assembly which is subjected to an electric potential gradient (operated in positive or negative mode). The electric field at the needle tip charges the surface of the emerging liquid which disperses into a fine spray or aerosol of charged droplets. Subsequent heating and/or use of an inert drying gas such as nitrogen or argon are typically employed to evaporate the droplets and remove solvent vapor before MS analysis. Variations on ESI systems optionally employ nebulizers, such as with pneumatic, ultrasonic, or thermal “assists,” to improve dispersion and uniformity of the droplets. Once ions are formed, they are then transported through a vacuum interface into a vacuum chamber containing a mass analyzer for MS analysis.
Mass spectrometers may employ one or both of two types of vacuum interfaces: the conduit and the orifice plate. Both serve to control the amount of matter that enters the vacuum chamber so that the pump responsible for generating a vacuum is not overwhelmed. Typically, the type of interface selected for any mass spectrometer depends on the overall design of the apparatus and the conditions under which ions are generated. For example, metallic or dielectric conduits such as those with an axial bore of capillary dimensions may be useful for restricting the number of molecules reaching the vacuum and for providing directionality to ion flow thereby effecting ion transport. In addition, conduits may be adapted to provide mass filtration, thereby removing background noise. The conduits can be heated to further effect droplet drying. However, conduits also have inherent drawbacks. For example, the total ion flux that emerges from the interface into the vacuum chamber may be too low for use with multi-sequence instruments.
In addition, the vacuum interface may comprise an opening in a plate that is charged with respect to the electrospray assembly. An opening in a plate may advantageously allow delivery of a large number of ions to the mass detector thereby resulting in a strong overall signal for any particular sample. Such a high ion flux is useful in multi-sequence instruments. However, there are many drawbacks to using a plate having an opening. For example, drying paths for a plate design are typically shorter than for a design that includes a conduit, and drying is therefore more difficult when a plate is used in place of a conduit. In addition, a charged plate usually requires a non-grounded electrospray assembly which may result in possible shock to a user of the instrument. The shock danger associated with using a charge plate is described with greater detail below.
To produce the electric potential gradient needed to ionize a sample, the electrospray assembly is insulated from the vacuum interface, and either the electrospray assembly, the vacuum interface, or both, are charged. Therefore, at least one of the electrospray assembly or the vacuum interface cannot be at ground potential. In addition, many mass spectrometers, particularly those using an orifice plate or a metal capillary, are designed such that the vacuum interface is electrically connected to ESI chambers that are fabricated from metals. Metals possess preferred structural and thermal properties, and use of plastics in such chambers often results in chemical contamination from outgassing. Subjecting an entire ionization chamber to a high potential would require a more expensive power supply than charging only the electrospray assembly. Thus, it is typically the electrospray assembly that is charged to a higher potential with respect to the rest of the mass spectrometer.
However, there are several drawbacks in using a charged electrospray assembly. First, an electrospray assembly at a high voltage to ground poses a possible shock hazard to the operator during its operation. The risk of electrical shock may result in operator reluctance in performing necessary routine adjustment and maintenance to ensure optimal operation of the electrospray assembly. As a result, the accuracy and the reliability of data from the mass spectrometer are compromised. In addition, an electrospray assembly may be adapted to be connected to other devices such as capillary electrophoresis systems or planar chips, and a charged electrospray assembly may interfere with operation of such devices. Moreover, liquid is often passed through the electrospray assembly during operation, and the liquid provides a medium through which electric current will flow. Thus, the power supply used to charge the electrospray assembly must be able to compensate for this leakage current.
Mass spectrometers having a substantially grounded electrospray assembly are not unknown in the art. For example, U.S. Pat. No. 5,838,003 to Bertsch et al. pertains to a mass spectrometry system having an electrospray ionization chamber incorporating an asymmetric electrode, wherein an electrospray assembly is described that may be operated at approximately ground potential in conjunction with a capillary operated at a high voltage. Because the housing of the chamber is at approximately ground potential, the capillary must be composed of a dielectric material or be electrically insulated from the housing. In addition, a capillary may disadvantageously remove ions traveling therethrough, reducing the number of ions available to produce a spectrum.
Thus, there is a need to provide a mass spectrometer with a grounded electrospray system that does not require any particular vacuum interface such as a dielectric capillary or other insulated vacuum interface between the ionization chamber and a vacuum chamber.